key: cord-0783706-yf550vvi
authors: Gao, Jie; Zeng, Li; Yao, Linlin; Wang, Ziniu; Yang, Xiaoxi; Shi, Jianbo; Hu, Ligang; Liu, Qian; Chen, Chunying; Xia, Tian; Qu, Guangbo; Zhang, Xian-En; Jiang, Guibin
title: Inherited and Acquired Corona of Coronavirus in the Host: Inspiration from the Biomolecular Corona of Nanoparticles
date: 2021-04-17
journal: Nano Today
DOI: 10.1016/j.nantod.2021.101161
sha: 4dcccabfe4236444f30e77f01349bfdabab2a218
doc_id: 783706
cord_uid: yf550vvi

Coronavirus is named for its crown shape. Encoded by the genetic material inherited from the coronavirus itself, this intrinsic well-known “viral corona” can be considered the “inherited corona”. After contact with mucosa or the entrance into the host, bare coronaviruses could become covered by a group of dissolved biomolecules to form one or multiple layers of biomolecules. Different from this inherited corona, the layers acquired from the surrounding environment could be named as “acquired corona”. We highlight here the possible role of the acquired corona absorbing onto the surface of coronaviruses, which will generate fresh insight into the nature of various coronavirus-host interactions.

Over the last year, the emergence of a novel infectious coronavirus in humans has resulted in the worldwide COVID-19 pandemic. There are four genera of coronavirus, including Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and

Deltacoronavirus. Belonging to the genus of Betacoronavirus, SARS-CoV-1, SARS-CoV-2, and MERS-CoV are able to infect humans and cause severe respiratory syndrome. The current outbreak of SARS-CoV-2 has resulted in the ongoing global COVID-19 pandemic. An efficient therapeutic strategy requires a better understanding of the interaction between SARS-CoV-2 and the host [1] .

Coronaviruses are a class of enveloped viruses with a positive-sense single-stranded ribonucleic acid (RNA) genome (Fig. 1 ). There are generally four types of protein in SARS-CoV-2, including the spike glycoprotein (S protein), membrane protein (M J o u r n a l P r e -p r o o f protein), nucleoprotein (N protein), and the envelope small membrane protein (E protein). SARS-CoV-2 can be transmitted via respiratory droplets, direct contact of skin mucous membrane and aerosol. In addition to the respiratory organs, genetic matters of SARS-CoV-2 could also be detected in the kidneys, liver, pancreas, GI tract, brain, nerves and heart, suggesting that SARS-CoV-2 could access most of the tissues. [3] Coronaviruses are named for their most prominent feature, the "crown of spikes" around the virion ("corona" means "crown" in Latin). This viral "corona" is composed of a lipid membrane and the M, E, and the trimeric S protein. Since this well-known corona is encoded by the genetic material inherited from the virion itself, it can be considered the "inherited corona". This inherited corona undoubtedly has a crucial role in the interaction of the virus with host cells the replication, and the construction of new virions [2] . The S protein mediates the entry of coronaviruses into the host cell through the attachment of the virus to cell receptors. The M protein maintains the structure of the viral envelope, through the interaction with other major structural proteins. As the smallest of the major structural proteins, the E protein also involves the coronavirus assembly. It is also involved in other aspects of the coronavirus replication cycle and the host cellular response to viral infection. All of the four proteins are critical in the biogenesis of new complete virions after entry into host cells. Within the inherited Through the binding to the RNA genome, the N protein has a function to construct the nucleocapsid. In host cells, the N protein is also responsible for the replication cycle and the virion formation. 

The virus-cell interaction can lead to various changes in the host's biology, such as stimulation of the host's immune system and potentially serious clinical symptoms [4] . Dissolved biomolecules in biological fluids are an important part of virus-cell interactions [5] . For instance, the complement protein C4 can inhibit infection through the direct inactivation of viral capsid proteins required for infection [6] . The interaction of soluble proteins with viruses can also enhance viral infectivity. For instance, as a dissolved biomolecule, prostatic acid phosphatase fragment in the semen of the host, can facilitate human immunodeficiency virus (HIV) infection [7] .

The interaction between soluble heparin-sulfonated proteoglycan cell surface attachment factors and virions initiates the infection of target cells by the human papillomavirus (HPV) [8] . Soluble biomolecules in host biofluids also play important roles in the response of host cells to the invasion of pathogens. It has been reported that coagulation factor X absorbed onto the surface of a virus could be internalized by macrophages along with the virion, and this intracellular translocation could trigger J o u r n a l P r e -p r o o f innate immune recognition [9] . The interaction of these biomolecules with coronaviruses could modulate the virus-cell interaction or cellular response.

As discussed above, some effects of soluble extracellular proteins on the behavior of infectious viruses have been revealed in recent decades. Nevertheless, after entering biological fluids, particles can not only absorb a single protein but also dynamically interact with hundreds to thousands of soluble proteins to form the "protein corona" [10] [11] [12] [13] . In addition to proteins, nanoparticles could also absorb other biomolecules, including lipids, sugars, and small molecules such as hormones and metabolites [14] [15] [16] [17] . These interactions could form one or multiple layers of biomolecules on the surfaces of the nanoparticles [18] , which is known as the "biomolecular corona" [19] . When entering into the natural environment, the binding or coating of biomolecules such as dissolved organic matter (DOM) on the surface of nanoparticles could form biomolecular corona or "eco-corona" [14, 17, 20, 21] . The components of this corona can endow invading particles with properties that are J o u r n a l P r e -p r o o f distinct from the intrinsic properties of bare nanoparticles. This affects their environmental behavior, and their interactions with cells, including particle recognition, cellular internalization, stimulation of intracellular signaling pathways, and subsequent biological activities [10, 22, 23] .

As natural particles at nanoscale, viruses can also interact with groups of molecules in biological fluids simultaneously as discussed above [6] [7] [8] [9] 24] . Recently, the understanding of the interaction of soluble proteins with viruses has begun to evolve from considering single proteins to encompassing multiple proteins [25] . Ezzat et al.

studied the protein corona absorbed onto respiratory syncytial virus (RSV) and herpes simplex virus type 1 (HSV-1) in different biological fluids [25] . Hundreds of proteins were found to absorb onto the viruses, and distinct profiles were observed because of the different surface properties of the two types of virus. This protein corona has important functions in viral infectivity, immune recognition, and induction of amyloid aggregation [25] .

Based on our previous understanding, it can be speculated that when coronaviruses are enveloped in different compartments, a dynamic biomolecular corona will form on the surface of the virion. Compared with the inherited corona described above, this "corona" is acquired, it is referred to as the "acquired corona" (Fig. 2) . The vast spectrum of biomolecules could form acquired corona (or eco-corona) on the surface of coronaviruses in the ambient environment, such as in the wastewater, inanimate surfaces, and oral droplets (Fig. 3A) . In the host environment, the acquired corona could form in different mocosa or pulmonary surfactant (Fig. 3B) . Because of the altered biomolecular components of in different J o u r n a l P r e -p r o o f biological fluids, the components of acquired corona may change dynamically when SARS-CoV-2 enveloped in different tissue microenvironments (Fig. 3C) . After the entry into the cells, the release into the blood stream, and the arrival into a targeting tissue, some biomolecules in the acquired corona of coronaviruses might be exchanged by the new biomolecules (Fig. 3C) . (Fig. 4) . When reach a given tissue, it is still unclear whether the acquired corona involves the observed different clinical syndromes in different tissues, such as gastrointestinal disease, pinkeye, runny nose, loss of taste and smell, heart failure, and kidney failure [28] . Recently, SARS-CoV-2 has been demonstrated to be able to transport to the nervous system through the penetration of the neural-mucosal interface in olfactory mucosa [29] .

Given that SARS-CoV-2 has the potential to attack the central nervous system [30] , After leaving hosts, the acquired corona is also an important factor in the environmental behavior of coronaviruses (Fig. 4) , which is important in the transmission and the infectivity of coronaviruses [32] [33] [34] [35] . Therefore, the acquired corona should be considered in order to in-depth understand the environmental behaviors of coronaviruses under a realistic environmental scenario outside of the host [34] . The acquired corona may form rapidly upon virus incorporation into biological fluids [38] , and revealed of corona-virus interactions should be evaluated. Because of the differences in the surface properties of engineered hard nanoparticles or other virions, the interface between coronaviruses and the acquired corona is also likely to be different. Better knowledge of the driving forces at the dynamic interface between viruses and soluble biomolecules will help in understanding the dynamic process of acquired corona formation (Fig. 5) . In situ coronavirus-biomolecule interactions in suspended biological fluids should also need to be studied to differentiate the soft acquired corona and hard acquired corona of coronaviruses [39, 40] .

J o u r n a l P r e -p r o o f 

Proc. Natl. Acad. Sci. USA, 105

Proc. Natl. Acad. Sci. USA